Cytochromes p450 as drug targets against mycobacterium tuberculosis and mycobacterium leprae.

Informazioni relative al progetto

ID dell’accordo di sovvenzione: HPMF-CT-2002-01633

Progetto chiuso

Data di avvio 1 Aprile 2002

Data di completamento 31 Marzo 2004

Finanziato da

• Programme for research, technological development and demonstration on "Improving the human research potential and the socio-economic knowledge base" (1998-2002)

Costo totale € 114 072,00

Contributo UE € 114 072,00

Coordinato da

UNIVERSITY OF LEICESTER
United Kingdom

Obiettivo

Mycobacterium tuberculosis (Mtb) is the biggest killer among infectious diseases. Multi-drug resistant strains are widespread. New antibiotic strategies are desperately needed to combat the deadly pathogen. The genome sequence of Mtb revealed that Mtb encodes a high number (~20) of cytochromes P450 (P450s). These enzymes have roles in sterol, lipid and and polyketide metabolism in the cell. The recent determination of the genome sequence of the leprosy pathogen (M. leprae) indicates a much smaller number of proteins encoded, with only a single P450 remaining. The remaining P450 is likely to be essential for bacterial viability. Azole drugs which inhibit activity of P450 enzymes also exhibit potent anti-mycobacterial effects. This suggests that azoles may be useful new drugs against these deadly pathogens. The major objectives of this proposal are the systematic study of the sole M. leprae P450 and its homologue in M. tuberculosis. This will involve protein expression and purification of the P450s, and detailed kinetic, spectroscopic and structural analysis of these enzymes. The substrate selectivity will be determined by spectral titrations and lipid analysis, and activity will be reconstituted with expressed redox partners. Azoles interactions will be also be examined. Collectively, these studies will allow fundamental understanding of these P450s' properties and their potential as drug targets.

Campo scientifico (EuroSciVoc)

CORDIS classifica i progetti con EuroSciVoc, una tassonomia multilingue dei campi scientifici, attraverso un processo semi-automatico basato su tecniche NLP.

• scienze mediche e della salute › scienze della salute › malattie infettive
• scienze naturali › scienze biologiche › biochimica › biomolecole › lipidi
• scienze mediche e della salute › medicina di base › farmacologia e farmacia › farmacoresistenza › multifarmacoresistenza
• scienze naturali › scienze biologiche › genetica › genomi
• scienze naturali › scienze biologiche › biochimica › biomolecole › proteine › enzimi

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Programma(i)

• FP5-HUMAN POTENTIAL - Programme for research, technological development and demonstration on "Improving the human research potential and the socio-economic knowledge base" (1998-2002)

Argomento(i)

Data not available

Invito a presentare proposte

Data not available

Meccanismo di finanziamento

RGI - Research grants (individual fellowships)

Coordinatore

UNIVERSITY OF LEICESTER

• Contributo UE: Nessun dato
• Indirizzo: The Adrian Building, University Road ; LE1 7RH LEICESTER ; Regno Unito
• Costo totale: Nessun dato